Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could reasonably be expected to be ascertained, understood and regarded as relevant by a person skilled in the art.
Articular cartilage is a highly specialized tissue that reduces joint friction at the extremities of long bones. It is predominantly avascular, aneural and alymphatic and it consists essentially of chondrocytes, some progenitor cells and an extracellular matrix (ECM). The ECM is composed of a network of collagens, in particular type II collagen, which gives the tissue its shape and strength, and proteoglycans, which give resistance to mechanical stress. Elastin fibres are also found, predominatly in the superficial zone.
The repair of damage to articular cartilage is one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of cartilage for repair.1 Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply.2 
Common treatments for cartilage repair include autologous chondrocyte transplantation (ACT), microfracture, mosaicplasty, and osteochondral allograft transplantation. ACT has been used for almost three decades to treat full-thickness chondral defects worldwide. However, inherent limitations of ACT include the low efficacy of cells due primarily to poor numbers obtained through biopsy and structural dissimilarity between the repaired tissue and native cartilage. Other drawbacks of these treatments include donor site morbidity, complicated surgical procedures, risks of infection, and graft rejection.3 
Due to its limited ability for self repair, cartilage is an ideal candidate for tissue engineering. Since collagen itself is a natural three-dimensional scaffold for cells in vivo, collagen isolated from animals has been used for a number of tissue engineering scaffolds in vitro, both in gel or solid forms. For example, type I collagen gel, when used as a three-dimensional scaffold for cell encapsulation, enhances the stability and differentiation of encapsulated cells.
One problem with collagen is that it alone cannot provide the compressive resilience required in articular cartilage that is normally provided by proteoglycan, especially aggrecan and other water binding connective tissue molecules. Further, when crosslinked, collagen may be difficult to inject at room temperature.
Unfortunately, because of several confounding characteristics of collagen, little progress has been made in producing hybrid scaffolds that incorporate both collagen and water binding synthetic molecules. In particular, due to its loose network structure, collagen is ineffective at retaining passively adsorbed molecules, which reside mostly in the highly hydrated spaces between collagen fibers, which lack attractive forces. Other problems, such as poor mechanical strength and the lack of tissue-specific adhesion and signalling molecules, also limit the use of purified collagen as a tissue engineering scaffold. In addition, the heterogeneous chemical composition of collagen and its complex molecular architecture present significant challenges when performing chemical reactions on collagen to modulate its biochemical properties.
On the other hand, synthetic scaffolds, such as hydrogels, offer better control of the matrix architecture and chemical composition. However, a number of limitations apply to the use of hydrogels that consist of synthetic molecules. First, without collagen or other ECM components, the necessary shape and strength characteristics of articular cartilage that arise from collagen cannot be derived from a synthetic hydrogel. Second, hydrogels are formed from polymers that must initially be crosslinked before the hydrogel can form. Crosslinking is an additional manufacture step that increases likelihood of contamination of the hydrogel, particularly with toxic components, or otherwise decreases the likelihood of biocompatibility with tissue. Third, synthetic hydrogels have low biological activities and therefore are limited in the extent to which they can provide a substrate for interaction with biological elements.
To date it has been difficult to provide a scaffold in which collagen and synthetic polymer are associated with each other, so as to provide a hydrogel having the strength, shape, and compressive resilience of articular cartilage. Simply applying a composition of collagen and synthetic polymer does not work because the collagen and polymer tend to dissociate in vivo so that a useful hydrogel for repair of articular cartilage is not formed.
Lee et al.4 describes a composite in which UV-crosslinked polymer is chemically linked to collagen modified protein (CMP). The composite forms a substrate on which cells may grow and lay down collagen. The collagen then binds to the CMP through non-covalent interactions, thereby forming a biosynthetic hydrogel composite in vivo. The problem with this approach is that it relies on cells existing in cartilage tissue to provide collagen. This either requires endogenous cells to infiltrate through articular cartilage, which is unlikely given that cartilage is essentially acellular, or the transplantation of chondrocytes or related cells. Further, the approach requires prior crosslinking of polymers to form the hydrogel.
There is a need for improved hydrogels that effectively model the shape, strength and resilience characteristics of articular cartilage.
There is a need for ECM-containing composites that effectively model the water binding and compressive resilience characteristics of articular cartilage as otherwise provided by the proteoglycan component of articular cartilage.
There is a need for synthetic hydrogels that effectively model the shape and strength characteristics of articular cartilage as otherwise provided by the collagen and ECM component of articular cartilage.
There is a need for synthetic hydrogels that can be formed without the use of chemical crosslinking, or crosslinking by UV irradiation or the like.
There is a need for hydrogels that bind to growth factors, drugs and the like, and that are a useful substrate for growth of cells thereon.
There is a need for compositions for repair of articular cartilage that are injectable at room temperature and that form a hydrogel at body temperature.